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This invention relates to pharmaceutical agents for the treatment of viral diseases, and more specifically, to pharmaceutical agents containing acyclovir and fusaric acid or derivatives thereof.
Acyclovir, 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)metyl]-6H-purin-6-one, has been used for the inhibition of herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV). Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against HSV-1, HSV-2 and VZV, which can be found in capsule, tablet, topical and suspension formulations. The following structural formula represents acyclovir: 
The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase encoded by HSV-1, HSV-2 and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In vitro, acyclovir triphosphate stops replication of herpes viral DNA. This is accomplished by: 1) competitive inhibition of viral DNA polymerase, 2) incorporation into and termination of the growing viral DNA chain and 3) inactivation of the viral DNA polymerase.
While the use of acyclovir is useful in the treatment of some herpes viruses, it has limitations related to tissue permeability and viral resistance that make its use less desirable. For example, acyclovir is not effective in topical formulation against herpes labialis and herpes genitalis. As such, acyclovir may not be used topically to effectively treat herpes labialis, herpes genitalis or other viral diseases, disorders, or conditions. Moreover, prodrugs of acyclovir have only minimal effects in herpes labialis. For example, the use of denavir to treat herpes labialis reduces the median duration of the illness by 6 hours. However, herpes labialis typically lasts in the range of about 6 to 7 days. Also, viral strains resistant to acyclovir and its prodrugs have emerged, which further limit its clinical usefulness.
Accordingly, there is a need to provide compositions that may be used topically to successfully treat a wide range of viral diseases.
In overcoming the above disadvantage, it is an object of the invention to produce compositions, which may be used topically to successfully treat a wide range of viral diseases.
Accordingly, and in one aspect of the invention, a composition including at least one nucleoside analogue inhibitor, a pharmaceutically acceptable salt, solvate, or prodrug thereof and fusaric acid, a derivative, or pharmaceutically acceptable salt of fusaric acid is provided.
In a second aspect, a pharmaceutical composition comprising the above-described composition of the invention and a pharmaceutically acceptable carrier is provided.
In a third aspect, a method of treating a viral disease, disorder, or condition comprising the administration of a pharmaceutically effective dose of the above-described pharmaceutical composition to a patient is provided.
In a fourth aspect, a topical preparation is provided that includes at least one above-described composition of the invention and a liquid vehicle.
In a fifth aspect, a systemic preparation is provided that includes at least one above-described pharmaceutical composition.
Other objects and features will be in part apparent and in part pointed out hereinafter.